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首页> 外文期刊>The Internet Journal of Pharmacology >Role of IGF-I in aspirin pretreatment in streptozotocin induced type-II diabetic rats
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Role of IGF-I in aspirin pretreatment in streptozotocin induced type-II diabetic rats

机译：IGF-I在链脲佐菌素诱导的II型糖尿病大鼠中阿司匹林预处理中的作用

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In the present study, we made an attempt to investigate role of insulin like growth factor-I (IGF-I) in aspirin pretreatment in streptozotocin induced type-2 diabetes mellitus in rats. Rat pups were divided in to four groups, on 5th day of their birth, group-I pups were received citrate buffer solution served as normal, group-II were treated only with streptozotocin (80mg/kg, i.p) served as diabetic, group-III & group-IV were treated with aspirin (10mg/kg/day, p.o) for one month (5-35 days) and two month (5-65) after streptozotocin served as treated groups. On 36 and 66 day, blood samples were collected from all animals and fasting blood sugar, fasting insulin, IGF-I, insulin resistance and insulin sensitivity levels were estimated. Results of 36 & 66 days blood samples of pups treated with streptozotocin alone and in combination with aspirin for one month and two months were shown significantly raised body weight, fasting blood glucose and insulin resistance levels (P=0.0005, p<.0001, p<.0001, P=0.0006, p<.0001, P=0.0030) and significantly lowered fasting insulin and insulin sensitivity levels when compared to the normal control pups (p<.0001, p<.0001, p<.0001, p<.0001, p<.0001, P=0.0068) respectively. Pups treated with aspirin for one month were shown significantly raised IGF-I levels but two months treatment were shown significantly lowered IGF-I levels when compared to the normal pups (p<.0001). The present study indicates that aspirin pretreatment seems to protect pancreas from damage caused by STZ and maintains glucose levels in diabetic rats and increases insulin sensitivity and reduces insulin resistance, this may a involvement of insulin like pathway particularly IGF-I. Introduction Type-2 diabetes mellitus is a metabolic disorder with characteristics of hyperglycemia and insufficiency of secretion or action of endogenous insulin [1]. Insulin resistance is one of the major characteristics of type 2 diabetes mellitus. If the insulin resistance can result from oxidative damage, then a prediction would be that chronic oxidative stress would lead to hyperinsulinaemia if plasma glucose is clamped at normal level by infusing the required insulin. Increased oxidative stress, defined as a persistent imbalance between the production of highly reactive molecular species (chiefly oxygen and nitrogen) and antioxidant defenses, is a widely accepted participant in the development and progression of diabetes and its complications [2]. Hyperglycemia was also found to promote lipid peroxidation of low density lipoprotein (LDL) by a superoxide-dependent pathway to generate free radicals [3]. Free radicals can be generated in glucose oxidation, which is believed to be the main source of free radicals, which are not degraded by catalase or glutathione peroxidase, and in the presence of transitional metals, can lead to production of extremely reactive hydroxyl radicals [4]. Aspirin is a derivative of salicylic acid, used as a NSAID, anti thrombotic, antioxidant and anti diabetic drug has new approach in type2 diabetes. Salicylates inhibit serine/ threonine caused insulin resistance and IKK-β activity and restore insulin sensitivity, both in-vitro and in vivo. Salicylate alters the phosphorylation patterns of IRS proteins, resulting in the decrease serine phosphorylation, increased tyrosine phosphorylation, and improved insulin action [5]. The principal mechanism of action of aspirin for its pharmacological actions is inhibition of arachidonate cyclooxygenase [6]. Cyclooxygenase (COX) is of two types namely COX-I & COX-II. COX-I is a constitutive enzyme expressed in most tissues including blood platelets and is involved in cell-cell signaling and tissue homeostasis. COX-II is induced in inflammatory cells when they are activated and is believed to be the enzyme that produces the prostanoid mediators of inflammation. Aspirin and also most of the non-steroidal anti inflammatory drugs (NSAIDS) in current use are inhibitors of both isoenzymes
机译：在本研究中，我们尝试研究胰岛素样生长因子-I（IGF-1）在链脲佐菌素诱导的2型糖尿病大鼠中阿司匹林预处理中的作用。将大鼠幼崽分成四组，在它们出生的第5天，将第I组幼崽接受柠檬酸盐缓冲溶液作为正常食物，第II组仅接受链脲佐菌素（80mg / kg，ip）进行糖尿病治疗，第链脲佐菌素作为治疗组后，III和IV组用阿司匹林（10mg / kg /天，口服）治疗一个月（5-35天）和两个月（5-65）。在第36天和第66天，从所有动物收集血液样品，并估计空腹血糖，空腹胰岛素，IGF-1，胰岛素抵抗和胰岛素敏感性水平。分别用链脲佐菌素和阿司匹林联合治疗一个月和两个月的幼犬的36和66天血样的结果显示体重，空腹血糖和胰岛素抵抗水平显着升高（P = 0.0005，p <.0001，p <.0001，P = 0.0006，p <.0001，P = 0.0030），与正常对照组相比，空腹胰岛素和胰岛素敏感性水平显着降低（p <.0001，p <.0001，p <.0001，p <.0001，p <.0001，P = 0.0068）。与正常幼犬相比，用阿司匹林治疗1个月的幼犬显示IGF-I水平显着升高，但两个月治疗显示IGF-I水平显着降低（p <.0001）。本研究表明，阿司匹林预处理似乎可以保护胰腺免受STZ损害，并维持糖尿病大鼠的葡萄糖水平，并增加胰岛素敏感性和降低胰岛素抵抗，这可能涉及胰岛素样途径，尤其是IGF-I。引言2型糖尿病是一种代谢异常，具有高血糖，分泌不足或内源性胰岛素作用[1]。胰岛素抵抗是2型糖尿病的主要特征之一。如果胰岛素抵抗是由氧化损伤引起的，那么可以预测到，如果通过注入所需的胰岛素将血浆葡萄糖控制在正常水平，则慢性氧化应激会导致高胰岛素血症。氧化应激的增加，被定义为高反应性分子物质（主要是氧和氮）的产生与抗氧化剂防御之间的持续不平衡，是糖尿病及其并发症[2]的发展和进程中被广泛接受的参与者。还发现高血糖通过超氧化物依赖性途径促进自由基生成，从而促进低密度脂蛋白（LDL）的脂质过氧化[3]。葡萄糖氧化中会产生自由基，这被认为是自由基的主要来源，自由基不会被过氧化氢酶或谷胱甘肽过氧化物酶降解，在存在过渡金属的情况下，会导致产生极活泼的羟基自由基[4]。 ]。阿司匹林是水杨酸的衍生物，用作非甾体抗炎药，抗血栓形成，抗氧化剂和抗糖尿病药物在2型糖尿病中具有新方法。水杨酸酯在体外和体内均可抑制丝氨酸/苏氨酸引起的胰岛素抵抗和IKK-β活性，并恢复胰岛素敏感性。水杨酸酯改变了IRS蛋白的磷酸化模式，导致丝氨酸磷酸化减少，酪氨酸磷酸化增加和胰岛素作用改善[5]。阿司匹林对其药理作用的主要作用机制是抑制花生四烯酸环氧合酶[6]。环氧合酶（COX）有两种类型，即COX-I和COX-II。 COX-1是在包括血小板在内的大多数组织中表达的组成型酶，并参与细胞信号传导和组织体内平衡。当COX-II被激活时，它们会在炎症细胞中被诱导，并且被认为是产生前列腺素类炎症介质的酶。阿司匹林以及目前使用的大多数非甾体抗炎药（NSAIDS）都是两种同工酶的抑制剂

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